What are the causes and treatment options for thrombocytopenia (low platelet count)?

Causes and Treatment of Thrombocytopenia

Causes of Thrombocytopenia

Thrombocytopenia should be approached based on its underlying mechanism, as this determines the appropriate treatment strategy and affects morbidity and mortality outcomes. The main mechanisms include:

1. Decreased Production

   • Bone marrow disorders (leukemia, myelodysplastic syndrome)
   • Viral infections (HIV, HCV)
   • Nutritional deficiencies (B12, folate)
   • Medications (chemotherapy agents)
   • Radiation exposure

2. Increased Destruction

   • Immune thrombocytopenia (ITP) - primary or secondary
   • Drug-induced immune thrombocytopenia
   • Heparin-induced thrombocytopenia (HIT)
   • Thrombotic microangiopathies (TTP, HUS)
   • Disseminated intravascular coagulation (DIC)

3. Splenic Sequestration

   • Hypersplenism
   • Portal hypertension
   • Liver disease

4. Dilutional

   • Massive transfusion
   • Pregnancy

Evaluation of Thrombocytopenia

When evaluating thrombocytopenia:

1. Confirm true thrombocytopenia - Exclude pseudothrombocytopenia by collecting blood in a tube containing heparin or sodium citrate 1

2. Determine acuity - Review previous platelet counts to distinguish acute from chronic thrombocytopenia 1

3. Assess bleeding risk - Platelet count thresholds:

   • 50 × 10^9/L: Generally asymptomatic

   • 20-50 × 10^9/L: May have mild skin manifestations (petechiae, purpura)
   • <10 × 10^9/L: High risk of serious bleeding 1

Treatment Approach

General Principles

Treatment should be initiated based on bleeding risk rather than absolute platelet count, with the goal of achieving a safe platelet count (≥50 × 10^9/L) to reduce bleeding risk rather than normalizing platelet numbers. 2

Treatment Based on Etiology

1. Immune Thrombocytopenia (ITP)

First-line treatment for ITP should include corticosteroids or intravenous immunoglobulin (IVIg), with IVIg preferred when rapid platelet count increase is needed. 2

• Corticosteroids:

  • Prednisone: 1-2 mg/kg/day for up to 14 days with rapid taper 2
  • High-dose dexamethasone: 40 mg/day for 4 days 2
  • Response rate: 72-88% within 72 hours 3

• IVIg:

  • Dosage: 0.8-1 g/kg as a single dose 2
  • Response rate: >80% within 1-2 days 3
  • Consider for patients with active significant bleeding or requiring rapid platelet increase 3

• Anti-D Immunoglobulin:

  • For Rh(D)-positive, non-splenectomized patients 2
  • Dosage: 50-75 μg/kg 2
  • Contraindicated if decreased hemoglobin due to bleeding or evidence of autoimmune hemolysis 2

Second-line treatments for persistent or chronic ITP include:

1. Thrombopoietin Receptor Agonists:

   • Romiplostim: Initial dose 1 mcg/kg weekly SC, adjust to maintain platelet count ≥50 × 10^9/L, maximum 10 mcg/kg 4
   • Eltrombopag: Initial dose 50 mg daily PO (25 mg for East/Southeast Asian patients or those with hepatic impairment) 5

2. Rituximab: Consider for patients with significant ongoing bleeding despite first-line therapy 2

3. Splenectomy: For patients who have failed corticosteroid therapy, with 72-93% response rates 2

2. Cancer-Associated Thrombocytopenia

For cancer patients with thrombocytopenia and thrombosis, anticoagulation should be adjusted based on platelet count thresholds. 3

• Platelet count ≥50 × 10^9/L: Full therapeutic anticoagulation
• Platelet count 25-50 × 10^9/L: Reduce LMWH to 50% of therapeutic dose or use prophylactic dose
• Platelet count <25 × 10^9/L: Temporarily discontinue anticoagulation 3

3. Viral-Associated Thrombocytopenia

• HCV-associated ITP: Consider antiviral therapy in the absence of contraindications; monitor platelet count due to risk of worsening thrombocytopenia with interferon 3
• HIV-associated ITP: Effective viral suppression using antiretroviral therapy can improve thrombocytopenia 3

Emergency Management of Severe Bleeding

For life-threatening bleeding in thrombocytopenic patients, use combination therapy including platelet transfusions, high-dose corticosteroids, and IVIg. 3

1. Platelet transfusions: Consider larger-than-usual dose (2-3 fold) for life-threatening bleeding 3
2. High-dose corticosteroids: IV administration for rapid effect
3. IVIg: 0.8-1 g/kg for rapid platelet increase 2
4. Antifibrinolytic agents: Consider as adjunct treatment 3
5. Recombinant factor VIIa: Consider in refractory cases, but note risk of thrombosis 3
6. Emergency splenectomy: Consider as a last resort in life-threatening situations 3

Special Considerations

1. Pediatric patients: Similar approach to adults but with more caution regarding long-term corticosteroid use 3

2. Pregnant patients: Treatment with corticosteroids or IVIg is recommended; delivery method should be based on obstetric indications 2

3. Thrombocytopenia with thrombosis: Consider conditions like antiphospholipid syndrome, HIT, and thrombotic microangiopathies 1

4. Procedural considerations: Ensure adequate platelet counts before invasive procedures; may require platelet transfusion 1

Monitoring

• Monitor platelet counts within 24 hours of initiating treatment, then daily until stable 2
• For patients on thrombopoietin receptor agonists, obtain complete blood counts weekly during dose adjustment phase, then monthly 4
• Educate patients about avoiding activities with high risk of trauma 2

Remember that the goal of treatment is to prevent significant bleeding complications rather than normalizing platelet counts, and treatment decisions should be guided by bleeding risk assessment and the underlying cause of thrombocytopenia.